Argyris PP, et al. - Researchers here focussed on calprotectin (S100A8/A9), a heterodimeric complex of calcium-binding proteins S100A8 and S100A9. Although adenocarcinomas and other cancers exhibit upregulation in calprotectin mRNA and protein levels, head and neck squamous cell carcinoma (HNSCC) shows a decline in these levels. S100A8 and S100A9 coregulate with gene networks controlling cellular development and differentiation, cell-to-cell signaling, and cell morphology, while S100A8/A9 appears to downregulate expression of invasion- and tumorigenesis-associated genes in HNSCC. In the tumor milieu, they observe a strong association of loss of S100A8/A9 with poor squamous differentiation and higher tumor grading, EGFR upregulation, increased DNA methylation, and, finally, poorer overall survival for patients with HNSCC.